...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Prostagladin D_2 is a mast cell-derived antiangiogenic factor in lung carcinoma
【24h】

Prostagladin D_2 is a mast cell-derived antiangiogenic factor in lung carcinoma

机译：前列腺素D_2是肺癌中肥大细胞衍生的抗血管生成因子

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

It is well established that prostaglandins (PGs) are involved in tumor angiogenesis and growth, yet the role of prostaglandin D_2 (PGD_2) remains virtually unknown. Here, we show that host he-matopoietic PGD_2 synthase (H-PGDS) deficiency enhances Lewis lung carcinoma (LLC) progression, accompanied by increased vas-' cular leakage, angiogenesis, and monocyte/mast cell infiltration. This deficiency can be rescued by hematopoietic reconstitution with bone marrow from H-PGDS-naive (WT) mice. In tumors on WT mice, c-kit+ mast cells highly express H-PGDS. Host H-PGDS deficiency markedly up-regulated the expression of proangiogenic factors, including TNF-α in the tumor. In mast cell-null Kit~(W-sh/W-sh) mice, adoptive transfer of H-PGDS-deficient mast cells causes stronger acceleration in tumor angiogenesis and growth than in WT mast cells. In response to LLC growth, H-PGDS-deficient mast cells produce TNF-a excessively. This response is suppressed by the administration of a synthetic PGD_2 receptor agonist or a degradation product of PGD_2,15-deoxy-△~(12'14)-PGJ_2. Additional TNF-a defi-ciency partially counteracts the tumorigenic properties seen in H-PGDS-deficient mast cells. These observations identify PGD_2 as a mast cell-derived antiangiogenic factor in expanding solid tumors. Mast cell-derived PGD_2 governs the tumor microenvironment by restricting excessive responses to vascular permeability and TNF-a production.
机译：众所周知，前列腺素（PGs）参与肿瘤血管生成和生长，但是前列腺素D_2（PGD_2）的作用实际上仍然未知。在这里，我们显示宿主造血PGD_2合酶（H-PGDS）缺乏会增强路易斯肺癌（LLC）的进展，并伴有血管渗漏，血管生成和单核/肥大细胞浸润的增加。可以通过用H-PGDS天真（WT）小鼠的骨髓进行造血重建来挽救这种缺陷。在野生型小鼠的肿瘤中，c-kit +肥大细胞高度表达H-PGDS。宿主H-PGDS缺乏明显上调了肿瘤中促血管生成因子（包括TNF-α）的表达。在肥大细胞无效的Kit（（W-sh / W-sh））小鼠中，H-PGDS缺陷型肥大细胞的过继转移比WT肥大细胞在肿瘤血管生成和生长中的促进作用更强。响应LLC增长，H-PGDS缺陷的肥大细胞过度产生TNF-α。通过施用合成的PGD_2受体激动剂或PGD_2,15-脱氧-△〜（12'14）-PGJ_2的降解产物可抑制该反应。额外的TNF-α缺乏部分抵消了H-PGDS缺乏的肥大细胞中所见的致瘤特性。这些发现将PGD_2确定为在实体瘤扩大中肥大细胞衍生的抗血管生成因子。肥大细胞衍生的PGD_2通过限制对血管通透性和TNF-α产生的过度反应来控制肿瘤的微环境。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号